This is a phase 2 trial to evaluate the safety and effectiveness of a new immunosuppressive drug, sirolimus, in patients with idiopathic and lupus membranous nephropathy. Patients (older than 13 years) were invited to participate if they had persistent nephrotic range proteinuria despite standard treatment with an angiotensin converting enzyme inhibitor or an angiotensin receptor blocker. Patients with persistent nephrotic range proteinuria are at increased risk for renal function deterioration as well as cardiovascular and thromboembolic complications. The target blood pressure was less than 125/75, as recommended by the Sixth Report Joint National Commission on the Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (NHLBI, NIH). Children less than 13 years were excluded because at the time this study was initiated, sirolimus had not been approved by the FDA in this age group and because a complete pharmacokinetics profile was not available in this age group. Furthermore, patients with advanced renal insufficiency (estimated glomerular filtration rate less than 30 mL/min/1.73 m2) were excluded because we anticipated that sirolimus would most likely be beneficial before progressive glomerular sclerosis and interstitial fibrosis had become the dominant (and probably irreversible) abnormalities. Patients with active infections, uncontrolled hypertension, chronic liver disease, cytopenias and a cancer diagnosis or recurrence within the preceding 5 years (excluding basal cell carcinoma of the skin) were excluded. Pregnant women, nursing mothers and individuals (men and women) not practicing birth control were excluded because the safety of sirolimus during pregnancy and infancy had not been determined. Patients could not take immunosuppressive agents or experimental medications of any type during the two-month period prior to initiating sirolimus, with two exceptions. First, patients with lupus membranous nephropathy were permitted to have received modest doses of corticosteroids (no more than the equivalent of prednisone 10 mg/day) for control of extra-renal manifestations of SLE during the two-month period prior to starting sirolimus. Second, patients with worsening nephrotic syndrome were allowed to start sirolimus after a shorter interval off other immunosuppressive agents. The loading dose of sirolimus was 2 mg every 4 hours for 3 doses (total dose of 6 mg) on the first day for adults and children greater than or equal to 40 kg. The initial maintenance dose of sirolimus for these individuals was 2 mg once daily. The initial and maintenance doses were modified for smaller individuals. The dose of sirolimus was adjusted to achieve a target level of 5 - 15 ng/mL during the first 6 months of the treatment period. The target level was increased to 10 - 20 ng/mL during the second 6 months if a complete remission had not been achieved by the end of the first 6 months. The sirolimus dose was held and/or reduced if certain toxic side effects were observed. Renal function, the degree of proteinuria and side effects were monitored closely throughout the study. Twelve patients have entered this study, and all patients have completed treatment or were withdrawn from sirolimus treatment because of side-effects and lack of efficacy. Only two patients have achieved a partial remission. Consequently, we are no longer recruiting or enrolling subjects into this study. These results were reported at the annual meeting of the American Society of Nephrology in November, 2008. Additional study and data analyses are ongoing.